Response surface methodology (RSM) is a collection of statistical design and numerical optimization techniques traditionally used to optimize industrial processes. In this paper, we demonstrate that the methodology can be successfully applied to the domain of networking. Specifically, we obtain increased throughput with a significant decrease in delay in a ns-2 simulation model of a mobile ad hoc network (MANET) by using RSM to optimize protocol interaction found by factor screening. Whether the experimentation is with a stochastic simulation model or a physical system, such as a MANET or a wireless sensor network test-bed, RSM provides a general and practical methodology to screen factors and robustly and jointly optimize responses.